Device for interacting with neurological tissue and methods of making and using the same

ABSTRACT

Described herein are microelectrode array devices, and methods of fabrication, assembly and use of the same, to provide highly localized neural recording and/or neural stimulation to a neurological target. The device includes multiple microelectrode elements arranged protruding shafts. The protruding shafts are enclosed within an elongated probe shaft, and can be expanded from their enclosure. The microelectrode elements, and elongated probe shafts, are dimensioned in order to target small volumes of neurons located within the nervous system, such as in the deep brain region. Beneficially, the probe can be used to quickly identify the location of a neurological target, and remain implanted for long-term monitoring and/or stimulation.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Stage of PCT InternationalApplication Number PCT/EP2011/055045, filed Mar. 31, 2011, which claimspriority to U.S. Provisional Application Ser. No. 61/320,089 filed Apr.1, 2010, the entire contents of the foregoing applications areincorporated by reference herein.

FIELD

The present disclosure relates generally to field of interacting withbiological tissue using electrical probes, and more particularly tointeracting with a neurological target through the use of microelectrodeprobes.

BACKGROUND

Neural recording and neurostimulation are categories of medical devicesthat are used to interact electrically with tissue. In the case ofneural recording, physiological measurements are performed ofneurological tissue that can diagnose, or treat, a patient. In the caseof neurostimulation, electric charge is transferred to the tissue inorder to create a therapeutic outcome, or to generate a diagnosis.Neural recording and neurostimulation devices are used today in thecochlea, the retina, the peripheral nervous system, the spine, thebrain, and other parts of the body.

In a particular application where both neural recording andneurostimulation are utilized, conductive electrodes are placed incontact with deep brain structures in order to treat certainneurological conditions. In the case of stimulating the PedunculopontineNucleus, for example, as described in U.S. Pat. No. 6,356,784, thetherapy can treat the symptoms of Movement Disorders such as Parkinson'sdisease. In the case of stimulating Brodmann Area 25, for example, asdescribed in U.S. Pat. No. 7,346,395, the therapy can treat the symptomsof Mood and Anxiety Disorders.

Generally, neural recording is performed in deep brain structures bysurgically inserting conductive electrodes and amplifying neurologicalsignals using external electronic equipment. Neurostimulation, isperformed by surgically implanting conductive electrodes in the target,and using an implantable pulse generator to apply electrical signals tothe conductive electrodes.

In some cases, such as described in U.S. Pat. No. 6,016,449, a systemhas been developed where both neural recording and neurostimulationfunctions are available in a single, long term implantable, device.

In most techniques, the electrodes used for neural stimulation that areplaced in contact with tissue have been metallic, cylindrical, with verysharp distal ends. In most cases, they only contain one microelectrode,which severely limits the amount of physiological information that canbe collected from the patient.

In other techniques, the electrodes used for neurostimulation that areplaced in contact with tissue have been metallic, cylindrical, andrelatively large in size (e.g., 1.27 mm in diameter and 1.5 mm inlength). In most cases, there are four or eight cylindrical electrodesplaced on a common axis. The stimulation methods are generally invasive,such as with the electrodes used in Deep Brain Stimulation, and theelectrode lead is generally attached implantable pulse generator.

Furthermore, advances in micromachining technology have developed wholenew applications for medical devices, and in particular, implantabledevices such as for the treatment and diagnosis of neurologicaldisorders.

Advances in the imaging of tissue have elucidated the function andanatomy of brain and nervous tissue, permitting the development of newtherapies which include electrical stimulation methods. A number ofresearch groups have reported on different approaches for imagingmethods, and the construction of implantable devices to delivertherapies. The imaging methods are generally extra-corporeal, andinvolve large and/or sophisticated equipment such as Magnetic ResonanceImaging systems.

One of the great challenges for clinicians delivering electricalstimulation therapy is in localizing the correct location for electrodeplacement, and then confining the stimulation field to the appropriateanatomical target to deliver the therapy, without inducing side effects.Clinicians generally combine pre-operative navigational planning derivedfrom Magnetic Resonance Imaging and/or Computed Tomography scan imagingsystems, with intra-operative microelectrode recordings ofelectrophysiological phenomenon to find and locate the optimal target.

Volumes of anatomical interest are commonly found using microelectroderecording techniques which involve invasively inserting metal tips tofind the area of interest by its electrophysiological activity. This maybe uncertain, time consuming, and repetitive insertions may be hazardousto patient health.

Unfortunately, there are several limitations to current practiceincluding uncertainty, discomfort for the patient, and a heavy financialburden to deliver the therapy. These factors can render the therapy lessattractive to clinicians, patients and payers.

It would be a very useful advancement in the art of neural recording andneurostimulation device technology and in the practice of functionalneurostimulation if the same device could image a volume of braintissue, and stimulate the same volume of tissue with precision andsafety.

There are many other medical applications for the present device, suchas detecting malignant tissue within healthy tissue.

SUMMARY

The present disclosure provides a design and method which permit theimaging of small volumes of tissue along with the capability ofstimulating precise areas within the volume of tissue. The imagingmethod presents an advancement over conventional methods that haverelied on expensive and low resolution systems. The stimulation methodpresents an advancement over conventional techniques which have notpermitted the precise steering of electrical fields into the optimaltissue activation volume required to deliver effective therapy.Combined, the imaging and stimulation method offers, for the first time,precise and high resolution stimulation of tissue in specific areas andvolumes.

The disclosed devices and methods have special applications in medicaluse, particularly in the treatment of neurological disorders.Embodiments provide an unprecedented resolution in the imaging of tissuevolumes by detecting local differences in electrical characteristics. Inthis way, some embodiments provide an imaging device, which whileinvasive and constrained in use, is able to provide a highly accurateregistration of the imaged volume. The image registration permits theidentification of anatomical structures, their surfaces and volumes, andtheir electrical characteristics such as, but not limited to,permittivity and conductivity.

When combined with stimulation methods, the device permits stimulationwithin specific regions, surfaces, and volumes of the registered image.The presently disclosed devices and methods provide the clinician and/orsurgeon a tool by which they can both visualize the tissue of interest,and stimulate specific areas within it. This greatly increases theaccuracy and safety of a surgery along with an improvement in thechronic therapeutic effects of stimulation.

The use of localized tomographical imaging to determine implant locationand stimulation volume is a unique and important advancement in thefield of neurological devices. Following the present disclosure, for thefirst time, clinicians will be able to substantially decrease theuncertainty in device placement, and increase the specificity of thelocation of stimulation.

The techniques described herein enjoy a number of advantages overconventional techniques to image tissue. Conventional methods in imagingrequire expensive equipment installations and resolution is increased byhigh field strengths in the case of Magnetic Resonance Imaging, or highX-ray dosages in the case of Computed Tomography scans. These highfields are not compatible with implantable devices containing metallicfeatures, and artifacts caused by devices translate to image drift,errors, or decreased resolution in the registered image.

By bringing the imaging device into contact with the volume of interest,and measuring local differences in electrical characteristics of thevolume, the some embodiments provide for images of unprecedentedresolution and fidelity.

Likewise, the techniques for stimulation described herein enjoy a numberof advantages over conventional efforts to stimulate tissue in a highlylocalized manner Conventional methods rely on implantable devices withelectrical leads often composed of cylindrical contacts, or metal tips.Most methods rely on stimulation volumes extending only outwards fromthe device, as in the case of a cylindrical device.

One possible approach to this issue is the use of smaller electrodes, inorder to stimulate with greater precision. However, there are practicallimitations in surgery which prevent the clinician from preciselytargeting the intended region. The image registration is often performedbefore the surgery, and subsequently navigational software is used toplan the implant trajectory and location. One approach is to incorporatethe MRI into the surgery, and perform intra-operative imaging, however,this is economically unviable in many hospitals, and the low fieldstrengths required to maintain compatibility with the implanted deviceslimit the resolution which can be achieved. For example, a surgeon wouldimplant a cylindrical electrode lead after finding and confirming thestereotactic co-ordinates of the target site. As a more specificexample, a neurosurgeon might implant an electrode lead in theSubthalamic Nucleus (STN) to treat the symptoms of Parkinson's Disease.The surgeon might not be able to easily find the STN, and even morecommonly, might not be able to locate the area within the STN that theyseek to stimulate using electric current. Furthermore, if the clinicianseeks to stimulate only a specific area, surface, volume, or populationof neurons or fiber bundles in, around, or near the STN, it would not bepossible using today's technology because of the size and geometry ofexisting electrode leads, which are considerably larger than theaforementioned targets.

The presently disclosed devices and methods greatly improve currentpractice without fundamentally changing the surgical procedurescurrently in use. As an example, a neurosurgeon targeting the STN wouldimplant the device using stereotactic co-ordinates very close to theSTN. The surgeon would then deploy the several prongs from the deviceinto and around the STN. The imaging method would be performed, whichwould provide the surgeon with a highly localized and high resolutionimage of the volume of tissue within the prongs of the device. The imagewill consist of a 2D or 3D tomography of the volume of tissue. The imageis constructed using the differences in electrical characteristics ofthe volume such as, but not limited to, conductivity, permittivity,conductivity and/or permittivity anisotropy. The image can thereforeprovide information about, but not limited to, the location anddirection of fiber tracts, neural cell density, the interface betweengrey and white matter. The image is created using electrical impedancetomography techniques which involve a sequence of steps by which currentis applied between two electrodes and a potential difference ispreferably detected across two different electrodes, or the sameelectrodes. By repeating this procedure across all the electrodes in theperiphery of the imaged volume, an image can be registered with thetomographic data using any one of a number of image reconstructiontechniques and algorithms.

Once the image has been registered, and the clinician can visualize whatthe device's exact location is, electrical stimulation can be applied tospecific areas of the volume using the principles of neurostimulationand the superposition of electric fields. The clinician can then steerthe stimulation field, and the volume of tissue activation, toparticular areas of the volume. For example, the image might display theinterface between the surface of the STN and fibers that are projectingfrom it, or to it. The clinician can then choose to stimulate thissurface and the volume of activation is directed there by combiningsignals from several electrodes on the device prongs.

As a result, a previously inaccessible region can be quickly located,and stimulated, thereby decreasing surgical times and increasing theefficacy of treatment. In contrast, conventional devices were limited bythe geometrical arrangement and size of electrodes, and by the lack ofsimultaneous or in-situ imaging when stimulating.

Another serious limitation to conventional devices is post-implantationmovement. A patient that is reacting positively to the stimulationtherapy might experience a movement of their electrode afterimplantation and thus, an immediate decrease or full halt in efficacyand the possible introduction of side effects. With the present device,if a device shift occurs, the volume of interest can be re-imaged, andthe stimulation volume can be re-directed to the proper region.

The presently described devices and methods benefit from the ability ofmodern microfabrication techniques to facilitate the construction of thedevice. Recent advances in surface micromachining permit variouselectrode geometries consisting of favorable materials such as Platinumand Platinum-Iridium to be manufactured. The electrode substrates canthen be assembled onto cut cylindrical components which consist of theprongs of the device. This assembly is further contained in animplantable catheter from which the prongs would extend during surgery.

In one aspect, an implantable neurological probe is disclosed including:an elongated probe assembly; at least one protruding shafts arranged atthe distal end of the elongated probe assembly; a plurality ofmicroelectrode elements arranged on the surface of the protrudingshafts; at least one electrical contact arranged proximally along theelongated probe assembly; and at least one electrical conductor inelectrical communication between at least one of the microelectrodeelements and the at least one electrical contact.

In some embodiments, the protruding shafts can be reversibly retractedwithin the elongated probe assembly. In some embodiments, the elongatedprobe shaft is configured for insertion into a human body using anaccepted procedure for insertion of deep brain stimulation leads. Insome embodiments, the diameter of the elongated probe assembly isbetween 1 mm and 3 mm.

In some embodiments, at least one of the plurality of microelectrodeelements is a stimulating electrode and at least one of the plurality ofmicroelectrode elements is a detecting electrode. In some embodiments,at least one of the plurality of microelectrodes elements is both astimulating electrode and a detecting electrode.

In some embodiments, each microelectrode element is formed on aconductive film, and where each microelectrode element is embeddedwithin two isolating substrates. In some embodiments, the microelectrodeembedded substrate is formable into a cylindrical assembly. In someembodiments, the protruding shafts can be formed to bend radial from thelongitudinal axis of the cylindrical assembly. In some embodiments, oneof the protruding shafts is longitudinal and centered along thelongitudinal axis of the cylindrical assembly. In some embodiments, theprotruding shafts are stiffened by a supporting member. In someembodiments, the longitudinal protruding shaft is stiffened by asupporting member.

In another aspect, a method for finding a neurological target including:implanting a neurological probe within a vicinity of a neurologicaltarget site, the neurological probe including an elongated cylindricalmember, a plurality of protruding shafts, a plurality of microelectrodeelements on each protruding shaft, at least one electrical contactarranged proximally along the probe shaft, and at least one electricalconductor in electrical communication between at least one of theplurality of the microelectrode elements and the at least one electricalcontact; retracting the protruding shafts within the elongatedcylindrical member before surgical implantation; expanding theprotruding shafts in the vicinity of the neurological target sitefollowing implantation; recording electrophysiological signals from theneurological target site using at least one of the microelectrodeelements on at least one of the protruding shafts; and stimulating theneurological target using at least one of the microelectrode elements onat least one of the protruding shafts.

In some embodiments, the protruding shafts are retracted within theelongated cylindrical member using a flexible pull wire situated in alumen of the elongated cylindrical member. In some embodiments, theprotruding shafts are expanded from within the elongated cylindricalmember using a rigid, or semi-rigid, push rod situated in a lumen of theelongated cylindrical member. In some embodiments, the act ofpositioning the distal end of the neurological probe includes recordingneural activity detected by at least one of the plurality ofmicroelectrode elements and repositioning the distal end of theneurological probe as required, until the recorded activity isindicative of the distal end of the elongated probe shaft being locatedsufficiently at the neurological target site.

In some embodiments, the act of positioning the distal end of theneurological probe includes stimulating neural activity by applyingelectrical signals to at least one of the plurality of microelectrodeelements on at least one of the plurality of protruding shafts,performing a clinical evaluation of the efficacy on the stimulation sitein the implanted patient, and repositioning the distal end of theneurological probe as required, until the patient's response isindicative of the distal end of the elongated probe shaft being locatedsufficiently at the neurological target site.

In some embodiments, the act of positioning the distal end of theneurological probe includes inhibiting neural activity by applyingelectrical signals to at least one of the plurality of microelectrodeelements on at least one of the plurality of protruding shafts,performing a clinical evaluation of the efficacy on the inhibition sitein the implanted patient, and repositioning the distal end of theneurological probe as required, until the patient's response isindicative of the distal end of the elongated probe shaft being locatedsufficiently at the neurological target site.

In another aspect, a method is disclosed for finding a neurologicaltarget including: implanting a neurological probe within a vicinity of aneurological target site, the neurological probe including an elongatedcylindrical member, a plurality of protruding shafts, a plurality ofmicroelectrode elements on each protruding shaft, at least oneelectrical contact arranged proximally along the probe shaft, and atleast one electrical conductor in electrical communication between atleast one of the plurality of the microelectrode elements and the atleast one electrical contact; retracting the protruding shafts withinthe elongated cylindrical member before surgical implantation; expandingthe protruding shafts in the vicinity of the neurological target sitefollowing implantation; applying an oscillating electric current betweenat least two of the microelectrode elements on at least one of theprotruding shafts; and detecting an electric voltage between at leasttwo of the microelectrode elements on at least one of the protrudingshafts.

In some embodiments, the act of applying oscillating currents anddetecting electric voltages is performed to image the electricalcharacteristics of the volume of neurological tissue between theprotruding shafts.

In another aspect, an implantable neurological probe is disclosedincluding: an elongated shaft having a distal end and an internal lumen;a support cylinder slidingly disposed in only a distal portion of theinternal lumen; a plurality of shafts coupled to the support cylinderand arranged to be selectively extended from the distal end of theelongated shaft; a plurality of microelectrode elements disposed on eachof the plurality of shafts, the microelectrode elements including aplanar substrate having an insulative layer and a plurality ofconductive traces disposed on the insulative layer, a stylet removablydisposed in the internal lumen and configured to contact the supportcylinder to selectively extend the plurality of shafts duringimplantation; and a pull wire coupled to the support cylinder toselectively retract the support cylinder and plurality of shafts withinthe internal lumen.

Some embodiments include a push-pull rod which includes the pull wireand the stylet.

In some embodiments, the elongated shaft is configured for insertioninto a human body using an accepted procedure for insertion of deepbrain stimulation leads.

In some embodiments, the diameter of the elongated shaft is between 1 mmand 3 mm.

In some embodiments, at least one of the plurality of microelectrodeelements is a stimulating electrode and at least one of the plurality ofmicroelectrode elements is a detecting electrode. In some embodiments,at least one of the plurality of microelectrodes elements is both astimulating electrode and a detecting electrode.

In some embodiments, each microelectrode element is formed on aconductive film, and where each microelectrode element is embeddedwithin two isolating substrates.

In some embodiments, the microelectrode embedded substrate is formableinto a cylindrical assembly.

In some embodiments, the protruding shafts can be formed to bendradially from the longitudinal axis of the cylindrical assembly.

In some embodiments, one of the protruding shafts extends and iscentered along the longitudinal axis of the cylindrical assembly.

In some embodiments, the protruding shafts are stiffened by a supportingmember. In some embodiments, the longitudinal protruding shaft isstiffened by a supporting member.

In another aspect, an implantable neurological probe is disclosedincluding: an elongated shaft having a distal end and an internal lumen;a plurality of shafts arranged to be selectively extended from thedistal end of the elongated shaft; and a plurality of microelectrodeelements disposed on each of the plurality of shafts, the microelectrodeelements including a planar substrate having an insulative layer and aplurality of conductive traces disposed on the insulative layer. In someembodiments, the plurality of shafts define a substantially cylindricalvolume when fully extended.

In some embodiments, the elongated shaft is configured for insertioninto a human body using an accepted procedure for insertion of deepbrain stimulation leads.

In some embodiments, the diameter of the elongated shaft is between 1 mmand 3 mm.

In some embodiments, at least one of the plurality of microelectrodeelements is a stimulating electrode and at least one of the plurality ofmicroelectrode elements is a detecting electrode.

In some embodiments, at least one of the plurality of microelectrodeselements is both a stimulating electrode and a detecting electrode. Insome embodiments, each microelectrode element is formed on a conductivefilm, and where each microelectrode element is embedded within twoisolating substrates. In some embodiments, the microelectrode embeddedsubstrate is formable into a cylindrical assembly. In some embodiments,the protruding shafts can be formed to bend radially from thelongitudinal axis of the cylindrical assembly. In some embodiments, oneof the protruding shafts extends and is centered along the longitudinalaxis of the cylindrical assembly. In some embodiments, the protrudingshafts are stiffened by a supporting member. In some embodiments, thelongitudinal protruding shaft is stiffened by a supporting member.

In another aspect, a method is disclosed for finding a neurologicaltarget including: implanting a neurological probe within a vicinity of aneurological target site, the neurological probe including: an elongatedshaft having a distal end and an internal lumen; a support cylinderslidingly disposed in only a distal portion of the internal lumen; aplurality of shafts coupled to the support cylinder and arranged to beselectively extended from the distal end of the elongated shaft; aplurality of microelectrode elements disposed on each of the pluralityof shafts, the microelectrode elements including a planar substratehaving an insulative layer and a plurality of conductive traces disposedon the insulative layer, a stylet removably disposed in the internallumen and configured to contact the support cylinder to selectivelyextend the plurality of shafts during implantation; and a pull wirecoupled to the support cylinder to selectively retract the supportcylinder and plurality of shafts within the internal lumen. In someembodiments, the method further includes: retracting the plurality ofshafts within the internal lumen before surgical implantation; extendingthe plurality of shafts in the vicinity of the neurological target sitefollowing implantation; recording electrophysiological signals from theneurological target site using at least one of the microelectrodeelements on at least one of the protruding shafts; and stimulating theneurological target using at least one of the microelectrode elements onat least one of the plurality of shafts.

In some embodiments, the method includes: after the acts of recordingand stimulating, retracting the plurality of shafts within the internallumen and removing the neurological probe from a subject.

In some embodiments, the protruding shafts are retracted using the pullwire. In some embodiments, the plurality of shafts are extended usingthe stylet. In some embodiments, the neurological probe includes apush-pull rod which includes the pull wire and the stylet

In some embodiments, the act of recording neurophysiological signalsincludes recording neural activity detected by at least one of theplurality of microelectrode elements and repositioning the distal end ofthe elongated shaft as required, until the recorded activity isindicative of the distal end of the elongated probe shaft being locatedsufficiently at the neurological target site.

Some embodiments include stimulating neural activity by applyingelectrical signals to at least one of the plurality of microelectrodeelements on at least one of the plurality of shafts, performing aclinical evaluation of the efficacy on the stimulation site in theimplanted patient, and repositioning the distal end of the elongatedshaft as required, until the patient's response is indicative of thedistal end of the elongated shaft being located sufficiently at theneurological target site.

Some embodiments include inhibiting neural activity by applyingelectrical signals to at least one of the plurality of microelectrodeelements on at least one of the plurality of shafts, performing aclinical evaluation of the efficacy on the inhibition site in theimplanted patient, and repositioning the distal end of elongated shaftas required, until the patient's response is indicative of the distalend of the elongated shaft being located sufficiently at theneurological target site.

In another aspect, a method is disclosed for finding a neurologicaltarget including: implanting a neurological probe within a vicinity of aneurological target site, the neurological probe including: an elongatedshaft having a distal end and an internal lumen; a support cylinderslidingly disposed in only a distal portion of the internal lumen; aplurality of shafts coupled to the support cylinder and arranged to beselectively extended from the distal end of the elongated shaft; aplurality of microelectrode elements disposed on each of the pluralityof shafts, the microelectrode elements including a planar substratehaving an insulative layer and a plurality of conductive traces disposedon the insulative layer, a stylet removably disposed in the internallumen and configured to contact the support cylinder to selectivelyextend the plurality of shafts during implantation; and a pull wirecoupled to the support cylinder to selectively retract the supportcylinder and plurality of shafts within the internal lumen. Someembodiments include retracting the plurality of shafts within theinternal lumen before surgical implantation; expanding the plurality ofshafts in the vicinity of the neurological target site followingimplantation; applying an oscillating electric current between at leasttwo of the microelectrode elements on at least one of the plurality ofshafts; and detecting an electric voltage between at least two of themicroelectrode elements on at least one of the plurality of shafts.

Some embodiments include: after the act of detecting, retracting theplurality of shafts within the internal lumen and removing theneurological probe from a subject.

Some embodiments include imaging the electrical characteristics of thevolume of neurological tissue between the plurality of shafts based onthe applied oscillating electric current and the detected electricvoltage.

In some embodiments, the neurological probe includes a push-pull rodwhich includes the pull wire and the stylet.

In another aspect, a method for finding a neurological target including:implanting a neurological probe within a vicinity of a neurologicaltarget site, the neurological probe including: an elongated shaft havinga distal end and an internal lumen; a plurality of shafts arranged to beselectively extended from the distal end of the elongated shaft; and aplurality of microelectrode elements disposed on each of the pluralityof shafts, the microelectrode elements including a planar substratehaving an insulative layer and a plurality of conductive traces disposedon the insulative layer, where the plurality of shafts define asubstantially cylindrical volume when fully extended. In someembodiments, the method includes: retracting the plurality of shaftswithin the internal lumen before surgical implantation; extending theplurality of shafts in the vicinity of the neurological target sitefollowing implantation; recording electrophysiological signals from theneurological target site using at least one of the microelectrodeelements on at least one of the protruding shafts; and stimulating theneurological target using at least one of the microelectrode elements onat least one of the plurality of shafts.

In some embodiments, the protruding shafts are retracted using a pullwire. In some embodiments, he plurality of shafts are extended using astylet. In some embodiments, the neurological probe includes a push-pullrod which includes the pull wire and the stylet.

In some embodiments, the act of recording neurophysiological signalsincludes recording neural activity detected by at least one of theplurality of microelectrode elements and repositioning the distal end ofthe elongated shaft as required, until the recorded activity isindicative of the distal end of the elongated probe shaft being locatedsufficiently at the neurological target site.

Some embodiments include: after the acts of recording and stimutating,retracting the plurality of shafts within the internal lumen andremoving the neurological probe from a subject

Some embodiments include stimulating neural activity by applyingelectrical signals to at least one of the plurality of microelectrodeelements on at least one of the plurality of shafts; performing aclinical evaluation of the efficacy on the stimulation site in theimplanted patient; and repositioning the distal end of the elongatedshaft as required, until the patient's response is indicative of thedistal end of the elongated shaft being located sufficiently at theneurological target site.

Some embodiments include inhibiting neural activity by applyingelectrical signals to at least one of the plurality of microelectrodeelements on at least one of the plurality of shafts, performing aclinical evaluation of the efficacy on the inhibition site in theimplanted patient, and repositioning the distal end of elongated shaftas required, until the patient's response is indicative of the distalend of the elongated shaft being located sufficiently at theneurological target site.

In another aspect, a method for finding a neurological target including:implanting a neurological probe within a vicinity of a neurologicaltarget site, the neurological probe including: an elongated shaft havinga distal end and an internal lumen; a plurality of shafts arranged to beselectively extended from the distal end of the elongated shaft; and aplurality of microelectrode elements disposed on each of the pluralityof shafts, the microelectrode elements including a planar substratehaving an insulative layer and a plurality of conductive traces disposedon the insulative layer, where the plurality of shafts define asubstantially cylindrical volume when fully extended. Some embodimentinclude retracting the plurality of shafts within the internal lumenbefore surgical implantation; expanding the plurality of shafts in thevicinity of the neurological target site following implantation;applying an oscillating electric current between at least two of themicroelectrode elements on at least one of the plurality of shafts; anddetecting an electric voltage between at least two of the microelectrodeelements on at least one of the plurality of shafts.

Some embodiments include imaging the electrical characteristics of thevolume of neurological tissue between the plurality of shafts based onthe applied oscillating electric current and the detected electricvoltage.

Some embodiments include: after the act of detecting, retracting theplurality of shafts within the internal lumen and removing theneurological probe from a subject

Various embodiments may include any of the above described elements orsteps alone, or in any suitable combination.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views.

FIG. 1 is a perspective view of one embodiment of an elongatedmicroelectrode assembly.

FIG. 2 is a perspective view of a portion of a human anatomyillustrating an exemplary elongated microelectrode assembly implantedtherein.

FIG. 3 is a perspective view of a portion of a human anatomyillustrating an exemplary microelectrode structure positioned at aneurological target.

FIG. 4A is a perspective view of a distal portion of the elongatedmicroelectrode assembly of FIG. 1 in the expanded position.

FIG. 4B is a perspective view of a distal portion of the elongatedmicroelectrode assembly of FIG. 1 in the retracted position.

FIG. 5 is a perspective view of a proximal portion of the elongatedmicroelectrode assembly of FIG. 1.

FIG. 6 is a planar view of an embodiment of a microelectrode array film.

FIG. 7 is a perspective view of the embodiment of a microelectrode arrayfilm of FIG. 6 after it has been assembled.

FIG. 8A is a planar top view of the microelectrode array film assemblyof FIG. 7.

FIG. 8B is a planar side view of the microelectrode array film assemblyof FIG. 7.

FIG. 9 is a planar frontal view of the microelectrode array filmassembly of FIG. 7.

FIG. 10 is a perspective view of the microelectrode array film assemblyof FIG. 7 in the retracted position.

FIG. 11 is a planer view of the retracted microelectrode array filmassembly of FIG. 10.

FIG. 12A is a perspective view of a central pin component.

FIG. 12B is a planar side view of the central pin component of FIG. 12A.

FIG. 13A is a perspective view of the outer legs component shown in theexpanded position.

FIG. 13B is a perspective view of the outer legs component shown in theretracted position.

FIG. 14 is a perspective view of the microelectrode array film assemblyof FIG. 7 shown assembled to the central pin component of FIG. 12A.

FIG. 15 is a perspective view of the microelectrode assembly of FIG. 14shown assembled to the flexible pull wire, and a microelectroniccomponent.

FIG. 16 is a perspective view of the microelectrode assembly of FIG. 15shown assembled to helical lead wires, and the outer legs component ofFIG. 13A.

FIG. 17 is a perspective view of the microelectrode assembly of FIG. 16shown assembled to an outer tubing and a stiff push rod.

FIG. 18 is a close-up perspective view of the microelectrode assembly ofFIG. 17 showing the flexible pull wire and the stiff push rod in moredetail.

FIG. 19A is a perspective view of the perforated end cap.

FIG. 19B is a planar view of the perforated end cap.

FIG. 20 is a cut-away perspective view of the microelectrode assembly ofFIG. 4A with segments of the perforated end cap and outer legs componentremoved.

FIG. 21 is a cut-away perspective view of the retracted microelectrodeassembly of FIG. 4B with segments of the perforated end cap and outerlegs component removed.

FIG. 22 is a planar view of the microelectrode assembly demonstratingmicroelectrode elements on the same plane.

FIG. 23 is a perspective view the assembly and planes of FIG. 22.

FIG. 24 is a perspective view of an alternative embodiment of theelongated microelectrode assembly of FIG. 1.

FIG. 25 is a planar front view of the alternative embodiment of FIG. 24.

FIG. 26 is a planar side view of the alternative embodiment of FIG. 24.

FIG. 27 is a perspective view of an alternative embodiment of theelongated microelectrode assembly of FIG. 1.

FIG. 28 is a planar side view of the alternative embodiment of FIG. 27.

FIG. 29 is a perspective view of an alternative embodiment of FIG. 1where the microelectrode arrays are placed on the outside of theprotruding shafts.

FIG. 30 is a planar back view of the alternative embodiment of FIG. 29.

FIG. 31 is a planar side view of the alternative embodiment of FIG. 29depicting separate stimulation and recording electrodes.

FIG. 32 is a detail perspective view of the alternative embodiment ofFIG. 29.

FIG. 33 is an additional detail perspective view of the alternativeembodiment of FIG. 29.

FIG. 34 is a component of the alternative embodiment of FIG. 29.

FIG. 35 is an additional component of the alternative embodiment of FIG.29.

FIG. 36 is yet an additional component of the alternative embodiment ofFIG. 29.

FIG. 37 is a perspective view of an alternative embodiment of FIG. 1where the protruding shafts have been implemented at two differentregions of the longitudinal axis.

FIG. 38A is a planar view of the alternative embodiment of FIG. 37.

FIG. 38B is an additional planar view of the alternative embodiment ofFIG. 37.

FIG. 39A is a perspective view of the microelectrode array film requiredin the assembly of the alternative embodiment of FIG. 37.

FIG. 39B is a perspective view of the protruding shaft support requiredin the assembly of the alternative embodiment of FIG. 37.

FIG. 40A is a perspective view of an alternative embodiment of FIG. 1where the microelectronic component is not required.

FIG. 40B is a perspective view of the microelectrode array film requiredin the assembly of the alternative embodiment of FIG. 40A.

FIG. 40C is a perspective view of an alternative embodiment of FIG. 1where the protruding shafts are not rigidified by the protruding shaftsupport.

FIG. 40D is a detail perspective view of the alternative embodiment ofFIG. 40C.

FIG. 41 is a schematic of a neural recording microelectronic circuit.

FIG. 42 is a schematic of a neural stimulation microelectronic circuit.

FIG. 43 is a schematic of a combined neural recording and stimulationmicroelectronic circuit.

FIG. 44 demonstrates the Electrical Impedance Tomography methoddescribed herein.

DETAILED DESCRIPTION

Described herein are microelectrode array devices, and methods offabrication and use of the same, to provide highly localized andefficient electrical stimulation of a neurological target, such asindividual neurons, groups of neurons, and neural tissue as may belocated in an animal nervous system, such as deep within a human brain.In small, difficult to find brain targets such as the PedunculopontineNucleus, or in targets that requires highly localized levels of neuralstimulation, such as the Subthalamic Nucleus, many microelectrodes arerequired in the brain region to find the target usingelectrophysiological recording. A higher number of microelectrodes willincrease the chance of finding the neurons required for therapeuticstimulation. The microelectrode, or group of microelectrodes, that areclosest to the target brain region will be used for chronic, therapeuticstimulation or inhibition.

The stimulation can be highly localized, because the microelectrodeelements can be as small as only 2 μm or large as 2 mm in either ofdiameter or width. The relative spacing between such microelectrodeelements can also be as small as only 2 μm or as large as 2 mmGenerally, microelectrodes of about 150 μm in diameter, with about a1000 μm spacing are particularly efficient in stimulating neural tissue.

An array of such microelectrode elements may consist of one or more suchelements (e.g., sixteen elements), each disposed at a respectiveposition, or site. This is in contrast to currently availablestimulation leads, such as the Model 3387 or Model 3389 DBS leadscommercially available from Medtronic, Inc. of Minneapolis, Minn. Suchcommercially available devices include relatively large, cylindricalelectrodes measuring about 1.5 mm in height, and having a maximum ofonly four electrodes in use today for deep brain stimulation.

Smaller microelectrode elements can be used to provide neurologicalstimulation that is highly localized and efficient because an array ofsuch microelectrodes can also be used to identify the stimulation regionof interest. For example, one or more microelectrode elements of such anarray of microelectrode elements can be used to record neuronal activityin the vicinity of the detecting/recording microelectrode elements. Suchrefinement offered by the relatively small size and/or spacing of themicroelectrode elements can be used to obtain a highly localized map ofneuronal activity in the region surrounding the implant. A suitablydimensioned microelectrode array having multiple microelectrode elementspositioned in a general vicinity of a neurological target, can be usedto locate a precise neurological target without further repositioning,by identifying those one or more microelectrode elements located in avery specific region of the neurological target. The microelectrodearray can be programmed to stimulate in a very specific region, forexample, using only a certain number of the microelectrode elements toactively stimulate the surrounding neurons and/or neuronal tissue, whileother electrode elements of the array remain inactive.

In the embodiments described, the microelectrode arrays are positionedin three dimensional space. This has been a previous limitation of suchmicroelectrode devices, which were usually implement in linear arrays,or two dimensional arrays on films. In the present embodimentmicroelectrode arrays are positioned along shafts which radiate from acentral lumen, in order to cover as much volume in the target regionwith microelectrode arrays.

In some embodiments, an elongated device including such microelectrodearrays having elements with relatively small size and/or spacing can beused to obtain a highly localized map of neuronal activity in the regionsurrounding the implant. For example, such a device configured with alinear array of microelectrodes positioned along a length of a distalend of the device can be placed into a patient's brain. Preferably, theelements of the microelectrode array envelop a region including theneurological target. Neurological activity can then be independentlydetected by one or more of the microelectrode elements. The detectedactivity may be captured in a recorder or display device, allowing aclinician to identify which one or more of the microelectrode elementsis positioned closest to the intended target. Knowing a respectivelocation of each of the microelectrode elements along the device, anddetermining the distance to a reference, such as the patient's skull, aprecise location of the target can be determined as the distance along atrajectory of the device, measured from the reference to the particularmicroelectrode element. Beneficially, location of the target can bedetermined without any repositioning of the elongated device, therebysimplifying the medical procedure and reducing patient risk.

In some embodiments, the device is for acute intra-surgical use, beingremoved after the target has been located, being replaced with a chronicprobe, positioned at the determined target location. Alternatively or inaddition, the device itself can be left in place as a chronic device,the same microelectrodes, or different ones, being used to record and/orstimulate the neurological target over an extended period.

One embodiment of a microelectrode device illustrated in FIG. 1 includesan elongated microelectrode lead assembly 100 sometimes referred to asan electrode lead. The microelectrode lead assembly 100 includes anexternal cylindrical member 102 including a microelectrode arrayassembly 150 located relative to a distal end and one or more electricalcontacts 106 located relative to a proximal end. The exemplarymicroelectrode lead assembly 100 includes one or more microelectrodearray shafts 160 adjacent to its distal tip. The microelectrode arrayassembly 150 has five protruding shafts 160, with disc microelectrodeelements disposed along an interior surface of an extended substrate. Inthe present embodiment four shafts protrude, to one of the anterior,posterior, lateral, or medial directions. An additional shaft protrudesalong the same longitudinal axis of the electrode lead, referred to asthe central shaft. The microelectrode lead assembly 100 also includeseight electrically conductive, cylindrical contacts, or contact rings(generally 106) distributed along a longitudinal axis of the proximalend of the assembly 100. In the exemplary embodiment, each of themicroelectrode elements is in electrical communication with a proximalcontact 106 via an embedded microelectronic element. In use, stimulationsignals are directed from an implantable pulse generator, or controllerto the microelectrode array. Additionally, in use, recording signals aredirected from the microelectrode array to an implanted or external datarecorder.

The microelectrode lead assembly 100 is preferably sized and shaped forits intended neurological application. For example, the microelectrodelead assembly 100 may be at least partially placed within the centralnervous system. Alternatively or in addition, the microelectrode leadassembly 100 may be at least partially placed within other parts ororgans of the body, such as the epidural space of the spine, or otherlocations within the peripheral nervous system, or within an organ suchas the liver or heart. Thus the diameter and length of themicroelectrode lead assembly 100 may vary depending on the particularanatomical target. Additionally, the configuration of the microelectrodearray shafts 160 is also sized and shaped for an intended neurologicaltarget. The number, shape, orientation, size, and spacing of themicroelectrode elements of the array can be defined in response to theintended neurological target.

In at least some embodiments one or more of the microelectrode elementsare sized and or spaced to record from and/or stimulate neurons. Themicroelectrode lead assembly 100 can be used to detect and/or recordneuronal activity at the neurological target. Neuronal activitynaturally occurring within the neurological target gives rise to localelectromagnetic fields that can be detected by one or more of themicroelectrode elements of the microelectrode array. For example,electric fields produced by neurons will polarize one or more of themicroelectrode elements. Such polarization gives rise to an electricalpotential with respect to a reference, such as electrical ground, oranother one of the microelectrode elements. Such electric activity canbe further conducted to one or more of the cylindrical contacts 106through the internal electrical conductors. One or more of thecylindrical contacts 106, in turn, can be connected to one or moreadditional medical devices for further processing of the detectedelectrical activity. For example, the cylindrical contacts 106 can becoupled to a display device or recording device for displaying and/orrecording electrical activity from the neurological target.

Alternatively or in addition, one or more of the microelectrode elementscan be used to electrically stimulate the neurological target. Forexample, one or more externally generated electrical signals can beapplied to one or more of the cylindrical contacts 106. These electricalsignals can be conducted through the internal electrical conductors toone or more of the microelectrode elements of the microelectrode array.Depending on the amplitude and polarity of the electrical signals, anelectrical field will be induced by the polarized microelectrodeelements. Electrical fields induced by such polarization can interactwith one or more neurons at the neurological target.

Alternatively or in addition, one or more of the microelectrode elementscan be used to perform Electrical Impedance Tomography of a neurologicaltarget or other bodily organ. For example, one or more externallygenerated electrical signals can be applied as a current to one or moreof the microelectrode elements. Depending on the physiologicalcharacteristics of the tissue being imaged, and depending on thefrequencies of the current signals applied, an electrical field will beinduced in the tissue. Electrical fields induced by such polarizationcan be detected by other microelectrode elements, thereby creating alocalized image of conductivity, permittivity, and/or other electricalcharacteristics.

Mechanical components of the implantable neurological lead assembly 100include the elongated outer cylindrical member 102, which can be asimple polymeric cylinder, or a rigid metallic or rigid polymericcylinder. The outer cylindrical member 102 can vary in length anddiameter but is generally at least about 28 cm long, (e.g., at least 20cm long, at least 25 cm long, at least 28 cm long, at least 30 cm long,etc.) and around 1.27 mm in diameter (e.g., in the range of 1.0-2.0 mmin diameter).

The neurological lead 100 can be implanted near a neurological target,such as a target brain structure, using common neurosurgical techniquessuch as stereotaxy or endoscopy. The microelectrode lead assembly 100can be inserted in its retracted state without support, or within asupporting cannula having an inner dimension slightly larger than theouter dimension of the device. The cannula, when used, would be removedonce the microelectrode lead assembly 100 has been suitably positioned.In some embodiments a lumen along the axis of the outer cylindricalmember 102 permits the insertion of a rigid stylet which renders themicroelectrode lead assembly 100 rigid during surgical implantation.This is particularly helpful during insertion, positioning andrepositioning of flexible embodiments of the microelectrode leadassembly 100. The stylet is removed after implantation leaving the probein its surgical target. In some embodiments the stylet is also a rigidpush rod, which is used to expand the microelectrode array shafts 160into the tissue. In some embodiments, the microelectrode lead assembly100 contains a flexible pull wire which is used to pull themicroelectrode array shafts 160 back into the retracted position. In yetadditional embodiments, the microelectrode lead assembly 100 containsonly one rigid push-pull rod which is used to both push and pull themicroelectrode array shafts 160 in its expanded and retracted positionrespectively. In yet additional embodiments, where the microelectrodelead assembly 100 is not intended to remain in the patient's brain aftersurgery, the rigid push-pull rod may be permanently attached to themicroelectrode array shafts 160.

A clinician can connect one or more of the microelectrode elements to adisplay unit or a recording unit through the cylindrical contacts 106.The recording unit, not shown, allows a clinician to identify certainregions of the brain according to their electrical activity. In someembodiments, such recording information can be processed automatically,through the use of a suitably programmed computer processor. Theelectrodes used to record from the brain can be the same electrodes asthose used to stimulate tissue. The recording electrodes can also beseparate from those used to stimulate the brain. This situation might bepreferred because electrodes destined for recording may be different insize and design than those for stimulation.

The operator can connect the electrodes to an external stimulationsource or an implantable source. In either instance, the source caninclude a pulse generator for applying signals to the electrode sites.The signals from such a pulse generator can be connected directly to theelectrodes, or they can be preprocessed using electronics embedded inthe device. The electronics can filter certain parts of the originalsignal. If there are more electrodes than signals, the electronics canroute or otherwise interconnect the stimulation source as necessary.

A perspective view of the portion of a human anatomy is illustrated inFIG. 2, showing implantation of an exemplary elongated microelectrodeprobe assembly 124 position for interaction with a neurological targetlocated deep within the brain. A distal portion of the microelectrodeprobe assembly 124 is positioned at the neurological target 130, in thisinstance located within the human brain 132. Several exemplarymicroelectrode array shafts 134 protrude from the distal portion of themicroelectrode probe assembly 124. In some embodiments the proximal endof the microelectrode probe assembly 124 is connected to a first medicaldevice 128. For example, the first medical device 128 may include anelectronic assembly implanted external to the brain 132 to minimizeinvasion into the body. Alternatively or in addition, a second medicaldevice, which again may include an electronic assembly such as a pulsegenerator 122 can be implanted at a remote portion of the subject body.As shown, a second electronic assembly 122 is implanted within a chestcavity 120. When one or more medical devices, such as the exemplarypulse generator 122 are located remotely in this manner, a cable 126 mayalso be implanted within the subject's body to interconnect the pulsegenerator 122 to the electronic assembly 128, when present or directlyto cylindrical contacts located at the proximal end of themicroelectrode probe assembly 124.

Referring now to FIG. 3, a cross-sectional view of a portion of ananatomy 148 is shown, illustrating an exemplary microelectrode probeassembly 140 positioned at a neurological target 148 (e.g., subthalmicnucleus, shown). The microelectrode probe assembly 140 includes fivemicroelectrode array shafts, 141A, 141P, 141L, 141M, 141C (generally141) protruding from a cylindrical containment structure 143. On eachmicroelectrode array shaft 141 are three microelectrode elements 145distributed linearly along the microelectrode array shaft 141.Preferably, the microelectrode probe assembly 140, and its protrudingmicroelectrode electrode arrays shafts 141 are shaped, spaced, and sizedto allow one or more of the microelectrode elements 145 to be positionedat the neurological target 149.

As illustrated, one or more of the microelectrode elements 145 of themicroelectrode probe assembly 140 are positioned in intimate contactwith the neurological target 149. In more detail, each microelectrodeelement 145 is a disc electrode along a shaft. It is understood thatsome microelectrode array shafts 141 can be in contact with theneurological target, while other microelectrode array shafts 141 are not(as shown). Additionally, it is understood that some microelectrodeelements 145 can be in contact with the neurological target, while othermicroelectrode elements 145 are not (as shown). In at least someembodiments, one or more of the microelectrode elements 145 are remotelyaccessible from a proximal end of the probe assembly 140 via one or moreelectrically conductive leads (not shown).

In at least some embodiments, selectable microelectrode elements 145 canbe activated to record and or stimulate the target 149. For example,recordings of neurological activity from microelectrode elements 145 incontact with the target 149 can be used to identify the location of thetarget 149 relative to the probe assembly 140 or relative to a standardstereotactic reference coordinate. As determined form the recordings,only those microelectrode elements 145 in contact with the target may beactivated to stimulate the target.

Any of the supporting structures described herein, such as thesupporting structure 140 illustrated here can be a ridged, or semi rigidstructure, such as a polymeric cylinder. Alternatively or in addition,the structure can be a flexible structure, such as one or more flexiblesubstantially non conducting substrate (i.e., a bi-electric ribbon) ontowhich the microelectrode elements 145 are formed as electricallyconductive film layers. The one or more microelectrode elements 145 arein communication with electronic circuitry (not shown) through one ormore electrical leads (not shown) that can be routed through an internallumen of a supporting structure 140 and/or formed using elongated filmlayers along a flexible, ribbon like supporting structure 140.

In some embodiments, the microelectrode elements 145 can be placed intothe brain generally for recording and/or stimulation of the cortex andfor deep brain stimulation and/or recording of neurological targetsincluding the subthalamic nucleus and the pedunculopontine nucleus. Themicroelectrode elements 145 can also be placed in other parts of thebody, such as the spine, the peripheral nervous system for neuralrecording and/or neural stimulation of such portions of an animalanatomy. Although microelectrodes are discussed generally throughout thevarious embodiments, there is no intention to limit the upper or lowersize of the microelectrodes. The devices and methods described hereinare generally scalable, with a microelectrode size determined accordingto the intended application. For at least some of the neurologicalapplications, microelectrodes are dimensioned sub-millimeter. In someembodiments, the microelectrodes are formed as planar structures havinga diameter of about 150 μm that are arranged in a linear array withcenter to center spacing of about 1000 μm. The planar structure of themicroelectrodes can have regular shapes, such as circles, ellipses,polygons, irregular shapes, or a combination of such regular and/orirregular shapes.

This probe assembly 140 is implantable near a neurological target, suchas a target brain structure, using common neurosurgical techniques suchas stereotaxy or endoscopy. The device might be inserted without supportor within a cannula which may have an inner dimension slightly largerthan the outer dimension of the device. Alternatively, or in additionto, the device may have a rigid stylet running along its central axiswith an outer diameter that is smaller than the inner diameter of anaxial lumen in the device. When used, such a cannula, or a stylet, isgenerally retracted once the device is in position.

The operator can connect the probe assembly 140 to a recorder unitconfigured to identify certain regions of the neurological target (e.g.,the brain) according to the electrical activity detected by the probeassembly 140. In some embodiments, the microelectrode elements 145 usedto record from the neurological target 149 can be the samemicroelectrodes as those used to stimulate the target in applications inwhich both recording and stimulation are accomplished. Alternatively orin addition, the microelectrode elements 145 used to record from theneurological target 149 can be separate microelectrode elements 145 fromthose used to stimulate the target 149. In some embodiments,microelectrodes destined for recording (e.g., 145) may differ in one ormore of size, shape, number, and arrangement from those microelectrodesdestined for stimulation, e.g., using different microelectrodes.

The microelectrode elements 145 configured for stimulation can beconnected to a stimulation source through one or more interconnectingleads. In some embodiment, at least a portion of the stimulation sourcecan be extracorporeal. Alternatively or in addition, the stimulationsource can be in vivo. Any implanted elements of the stimulation sourceare preferably fabricated and/or contained with a hermetically sealed,bio-compatible envelope. Such bio-compatible packaging of signal sourcesis well known, for example, in the area of artificial pacemakers. Thestimulation source, when provided, may be a controllable signalgenerator producing a desired signal according to a prescribed input.For example, the signal generator may receive an input indicative of adesired output stimulation signal frequency. Such output stimulationsignals can have a variety of wave forms, such as pulses, chargedbalanced pulses, sinusoidal, square wave, triangle wave, andcombinations of such basic wave forms.

In some embodiments, the stimulation source includes a pulse generatorfor applying signals to the microelectrodes site. The signals from thepulse generator can be connected directly to the microelectrodes, orthey can be preprocessed using electronics. In some embodiments, suchpreprocessing electronics are embedded within the implantable device.The preprocessing electronics can filter certain parts of an originalsignal, such as a cardiac pacemaker signal, in order to select preferredfrequency components of the original signal that are at or near a peakresistance frequency of the microelectrodes. For embodiments in whichthere are more microelectrodes than signals, electronics can route thestimulation signals to preferred one or more of the microelectrodes.

Referring now to FIG. 4A a more detailed view of a distal end of themicroelectrode probe assembly 100 is shown. The microelectrode arrayassembly 150 includes a perforated end-cap 190 which contains theprotruding microelectrode array shafts 160A, 160L, 160P, 160M, and 160C(generally 160). The microelectrode arrays shafts 160 are lettered A, L,P, M, and C in order to coincide with the anatomical convention ofAnterior, Lateral, Posterior, Medial, and Central positionsrespectively. Each microelectrode array shaft 160 contains threemicroelectrode elements 265 in a linear arrangement. The microelectrodeelements 265 on microelectrode array shaft 160M are shown and labeled265Ma, 265Mb, and 265Mc. Microelectrode element 265Ma is the most distalalong microelectrode array shaft 160M, whereas microelectrode element265Mc is the most proximal. Each microelectrode array shaft 160 containsthree microelectrode elements 265 on its interior surface.

Referring now to FIG. 4B a more detailed view of a distal end of themicroelectrode probe assembly 100 in the retracted position is shown. Inthis state, the protruding microelectrode shafts 160 have been retractedinto the interior of the perforated end-cap 190 and are completelycontained within the microelectrode array assembly 150. Also visible arethe perforations 192 on the perforated end-cap 190 which correspond toeach microelectrode array shaft 160. The perforations 192 are letteredA, L, P, M, and C in order to coincide with the anatomical convention ofAnterior, Lateral, Posterior, Medial, and Central positionsrespectively. The perforated end-cap 190 is attached to the outercylindrical member 102.

Referring now to FIG. 5 a more detailed view of the proximal end of themicroelectrode probe assembly is shown. The cylindrical contacts 106 arearranged along the longitudinal axis of the outer cylindrical member102. Each of the eight cylindrical contacts 106, 106 a through 106 h, iselectrically connected to a lead wire (not shown) which is incommunication with the distal end of the microelectrode lead assembly100. In the exemplary embodiment each cylindrical contact measures 1.27mm in diameter, and 2 mm in length. The cylindrical contacts 106 arespaced from each other by insulating cylindrical contacts 107 a through107 h (generally 107). In some embodiments there may only be onecylindrical contact 106, while in other embodiments there may be two ormore cylindrical contacts 106. Generally there are between four andeight cylindrical contacts 106.

The microelectrode lead assembly 100 contains one removable rigid pushrod 170, and one non-removable flexible pull wire 175. The rigid pushrod 170 is used to expand the microelectrode array assembly 150 into itsexpanded state. The flexible pull wire 175 is used to pull themicroelectrode array assembly 150 back into is retracted state. Asshown, the rigid push rod 170 is composed of three features. The firstfeature is a hollow rigid stylet 172 that is also used to straighten themicroelectrode lead assembly 100 during implantation. The second featureis a longitudinal slit 173 which permits access to the central lumen ofthe rigid stylet 172. The third feature is the push handle 174 whichpermits the operator to apply a pressure and expand the microelectrodearray assembly 150 at the distal end. As shown, the flexible pull wire175 has three features. The first feature is a flexible central wire 176which is permanently attached to the microelectrode array assembly 150at the distal end. The second feature is a pull handle 178 which theoperator can use to retract the microelectrode array assembly at thedistal end by pulling. The third feature is a hole 179 in the pullhandle 178 which the operator can use to facilitate the pulling actionrequired of the component. Together, push rod 170 and pull rod 175 areused in order to expand and retract the microelectrode array shafts 160and the distal end of the microelectrode lead assembly 100.

Referring now to FIG. 6 a more detailed view of the microelectrode arrayfilm 200 is shown in its non-assembled state. The microelectrode arrayfilm 200 is produced using a sequential production method where severalfilms are deposited one atop the other. The first film is a polymeric,isolating film such as polyimide. The second film is a conductive,preferably noble metallic film such as platinum. The second film isstructured in order to create metallic traces and discs. The third filmis a polymeric, isolating film, such as polyimide. The third and firstfilms are then structured to provide the outline shown in FIG. 6.Embedded metallic layers are not shown, while metallic discs andelectrical contacts are exposed. The microelectrode film shafts 260correspond each to one of the microelectrode array assembly shafts 160shown previously. The microelectrode film shafts 260 are numberedcorresponding to their appropriate shaft, Anterior, Lateral, Posterior,Medial, and Central as 260A, 260L, 260P, 260M, and 260C. Themicroelectrode film shafts 260 contain the microelectrode elements 265.The microelectrode elements 265 on microelectrode film shaft 260P arelabeled as an example, where 265Pa is the most distal microelectrodeelement and 265Pc is the most proximal microelectrode element. Thelength of microelectrode film shaft 260C and the spacing of itsmicroelectrode elements 265 differs slightly from the other geometriesbecause it forms part of the central microelectrode array shaft 160 andwill not be at an angle to the longitudinal axis of the microelectrodelead assembly 100.

The next feature on the microelectrode array film 200 is the distalstructural cylinder 210 which is shown in its flattened state, but onceassembled will be used to stabilize the film in its final assembly. Themicroelectronic platform 212 is where a subsequent microelectroniccomponent will be attached. The microelectronic component is explainedin detail below. It is preferably attached to the microelectrode arrayfilm 200 while it is still in its flattened state. On themicroelectronic platform 212 are arranged the microelectronic platformbond bands 270 which are used to electrically communicate themicroelectrode elements 265 to external equipment through themicroelectronic component. They are arranged in a two dimensional array.The central structural cylinder 214 which is shown in its flattenedstate, but once assembled will be used to stabilize the film in itsfinal assembly. The helical ribbon cable 216 which is shown in itsflattened state, but once assembly will be used to permit movement ofthe microelectrode array assembly 150 within the microelectrode leadassembly 100. The proximal structural cylinder 218 is shown in itsflattened state, but will be attached to an internal cylinder within themicroelectrode lead assembly 100 and is the only non-moving part of themicroelectrode array film 200. On the proximal structural cylinder 218are the proximal contact pads 208 which are used to communicate theelements of the microelectronic component to lead wires that communicatethe distal portion of the microelectronic lead assembly 100 to itsproximal portion.

FIG. 7 demonstrates the microelectrode array film 200 in its assembled,and expanded state. The central microelectrode film shaft 260C, and thefour microelectrode film shafts 260A, 260L, 260P, 260M are shown, withtheir respective microelectrode elements 265 on the interior of theassembly. The distal structural cylinder 210 is shown curled into itscylindrical state. The microelectronic platform 212 is shown bent it itshorizontal position. The central structural cylinder 214 is shown curledinto its cylindrical state. The helical ribbon cable 216 is shown curledand pulled into its assembled state. The proximal structural cylinder218 is shown curled into its position, with proximal contact pads 208exposed. The microelectrode array film 200 can be assembled into thisconfiguration in steps, or after assembly with subsequent components.

FIG. 8A is a planar side view of the microelectrode array film 200 inits assembled, and expanded state. The important features to note inthis view are the slits 211, 215, 219 in the structural cylinders 210,214 and 216 respectively which are present because of the curlingrequired to assemble the film into its position.

FIG. 8B is a planar top view of the microelectrode array film 200 in itsassembled, and expanded state.

FIG. 9 is a planar front view of the microelectrode array film 200 inits assembled, and expanded state. The position of the four angledmicroelectrode film shafts 260 are shown, and the interiormicroelectrode elements 265 are visible.

FIG. 10 demonstrates the microelectrode array film 200 in its assembled,and retracted state. The central microelectrode film shaft 260C, and thefour microelectrode film shafts 260A, 260L, 260P, 260M are shown, withtheir respective microelectrode elements 265 on the interior of theassembly. These microelectrode film shafts 260 have moved from theirangle position into a closed position. The structural cylinders 210, 214and 218 have not change in shape. Structural cylinders 210 and 214 havenot moved in position relative to each other. Structural cylinders 210and 214 have both moved closer to structural cylinder 218. This movementhas caused the reversible of the helical ribbon cable 216.

FIG. 11 demonstrates a planar side view of the microelectrode array film200 in its assembled, and retracted state. The anterior microelectrodefilm shaft 260A and the posterior microelectrode film shaft 260P are inparallel positions.

Referring now to FIG. 12A, a perspective view of the central pin 185 isshown. This pin will be assembled in a subsequent step to themicroelectrode array film 200. The central pin has several featuresincluding a protruding axial shaft 186, a cylindrical member 188, and alengthwise slit 189 on the cylindrical member 188. The protruding axialshaft 186 has a bend 187 which permits it to be positioned along thelongitudinal axis of the cylindrical member 188. Generally, thecomponent is formed from a rigid cylindrical material such as medicalgrade stainless steel which has been cut by a laser into the presentshape. FIG. 12B demonstrates a side view of the central pin 185.

Referring now to FIG. 13A, a perspective view of the expandable shaftsupport 180 is shown. The expandable shaft support 180 is composed ofcylindrical member 182, from which protrude four semi-rigid shafts intothe Anterior direction 181A, the Lateral direction 181L, the Posteriordirection 181P, and the Medial direction 181M. The semi-rigid shafts 181are expanded radially from the longitudinal axis of the cylindricalmember 182. Generally, the component is formed from a rigid cylindricalmaterial such as medical grade stainless steel which has been cut by alaser into the present shape. FIG. 13B demonstrates a perspective viewof the expandable shaft support 180 in its retracted position.

Referring now to FIG. 14, the central pin 185 is shown assembled ontothe central microelectrode film shaft 260C to form the centralmicroelectrode array shaft 160C.

Referring now to FIG. 15, the microelectronic component 300 has beenassembled onto the microelectronic component platform 212. Contact padson the microelectronic component 300 have been attached to theirrespective microelectronic contact pads 270 on the microelectrode arrayfilm. The proximal structural cylinder 218 has been attached and wrappedaround the internal elongated cylindrical member 103 which extends tothe proximal portion of the microelectrode lead assembly 100. The distalportion of the central pull wire 175 is visible. It is permanentlyattached to the interior of the central support cylinder 214 and is usedto pull the assembly into its retracted position.

Referring now to FIG. 16, microelectrode array film 200 has beenassembled onto the interior circumference of the expandable shaftsupport 180 forming the microelectrode array shafts 160. In addition,the helical lead wires 290 have been wound around the internalcylindrical member 103 and have been attached to their respectiveproximal contact pads 208.

Referring now to FIG. 17, the microelectrode array shafts 160 are shownwith the stiff push rod 170 in contact. The stiff push rod 170 is usedto push the assembly into its expanded position. Additionally, theassembly is shown with outer cylindrical member 102 in its assembledposition.

FIG. 18 is a close-up perspective view of the interior assembly todemonstrate the positions of the stiff push rod 175 and the flexiblepull wire 170.

FIG. 19A is a perspective view of the perforated end-cap 190 whichdemonstrates the perforations 192 from which the microelectrode shaftswill emerge. FIG. 19B is a planar cutaway view demonstrating the cavity191 within the perforated end-cap 190 in which the entire microelectrodearray shaft assembly 160 is housed.

FIG. 20 is a cut-away perspective view with several elements removed forclarity of the assembly in the expanded position. Part of the perforatedend cap 190 and the expandable shaft support 180 have been removed inorder to reveal the positions of the microelectrode component 300, andthe stiff push rod 170.

FIG. 21 is a cut-away perspective view with several elements removed forclarity of the assembly in the retracted position. Part of theperforated end cap 190 and the expandable shaft support 180 have beenremoved in order to reveal the positions of the microelectrode component300, and the stiff push rod 170. Most importantly, the microelectrodearray shafts 260 are contained within the interior of the perforated endcap 190, and the helical ribbon cable 216 has been reversible compressedinto is retracted position.

When the microelectrodes are in use, they are placed on the same plane,in order to improve the operator's understanding of anatomical placementof the electrophysiological recording, and or stimulation. FIG. 22 is aplanar view of the microelectrode assembly demonstrating microelectrodeelements on the same plane. FIG. 23 is a perspective view the sameassembly and same planes of FIG. 22. In this embodiment, the planes areseparated by 1 mm, and are parallel. This arrangement requires that themicroelectrode elements 265 on the central protruding shaft 160C have asmaller spacing than the microelectrode elements 265 on the anterior,lateral, posterior, medial protruding shafts 160A, 160L, 160P, 160M. Inthe present embodiment, it has been chosen that the protruding shaftsmake a 30° angle with the central shafts once expanded. In the expandedposition, the most distal microelectrode elements 265 of the fiveprotruding shafts 160 should all be on the same plane 400 a.Additionally, the central microelectrode elements 265 of the fiveprotruding shafts 160 should all be on the same plane 400 b.Furthermore, the most proximal microelectrode elements 265 of the fiveprotruding shafts 160 should all be on the same plane 400 c.

Additional Embodiments

In some embodiments the protruding shafts may be curved, or bent, into adifferent angle. This may have the advantage that the tips of theprotruding shafts can cover a greater volume. FIG. 24 demonstrates anembodiment of a distal microelectrode assembly 550 where the protrudingshafts 560 curl away from the longitudinal axis of the elongated probe.On each of the protruding shafts are four microelectrode elements. Insome embodiments the central pin may not be necessary, and theembodiment in FIG. 24 does not contain said central pin. FIG. 25 is aplanar view of the same embodiment, and FIG. 26 demonstrates anadditional view.

In some embodiments it is advantageous for the protruding shafts to bebent in such a manner that when in the expanded state, they remainparallel to the longitudinal axis of the elongated probe. Thealternative embodiment of a distal microelectrode assembly 650 shown inFIG. 27 demonstrates protruding shafts 660 that have been bent in orderto remain parallel to the longitudinal axis of the said assembly. Thiscreates a cylindrical volume of influence within the confines of thedevice. Additionally, the central protruding shaft 660C may consist of asingle cylindrical electrode, and not an array of microelectrodes. FIG.28 demonstrates this alternative embodiment in a planar side view.

In some embodiments it is advantageous for the microelectrode array filmto be positioned on the exterior of the protruding shafts. FIG. 29 is aperspective view of an alternative embodiment of a distal microelectrodeassembly 750 where the microelectrode elements are placed on the outsideof the protruding shafts. FIG. 30 demonstrates a planar back view of thealternative embodiment. FIG. 31 is a planar side view of the alternativeembodiment of FIG. 29 depicting separate stimulation and recordingelectrodes. In some embodiments it is advantageous for recordingmicroelectrode elements 766 to be smaller in diameter than thestimulation microelectrode elements 765. Additionally, stimulationmicroelectrode elements 765 may function advantageously with largereffective surface areas.

FIG. 32 is a detail perspective view of the alternative embodiment ofFIG. 29 with perforated end-cap removed. Due to the friction thatrepeated retraction and expansion of the protruding shafts may create onthe microelectrode array film, a slide guide 781 is introduced in thisembodiment. Additionally, as shown in FIG. 33, the central pin 781 isimplemented as a sharpened cylinder, on which a large microelectrodeelement 767 has been wrapped. Additionally, a central pin support 782 isintroduced which permits alignment and added robustness of the centralprotruding shaft 760C.

FIG. 34 demonstrates the required protruding shaft support 780 requiredto implement the alternative embodiment. FIG. 35 demonstrates the slideguide 781, and FIG. 36 depicts the central pin support 782.

In some embodiments it is advantageous to include protruding shafts anddifferent distal distances along the longitudinal axis of the elongatedmicroelectrode probe. FIG. 37 is a perspective view of an alternativeembodiment where eight protruding shafts have been implemented at twodifferent distal regions of the longitudinal axis. The componentsrequired to implement this embodiment are similar to the previousembodiments presented. Distal microelectrode assembly 850 is composed ofan elongated perforated end cap 890 which contains the microelectrodearray film 820 and protruding shaft support structure 880. Theprotruding shafts (generally 860) have been numbered according to theirproximal or distal position, as 860P or 860D in general. The protrudingshafts have been additionally numbered according to their anatomicalposition, anterior, lateral, posterior, and medial. For example, theproximal protruding shafts (generally 860P) have been numbered 860PA,860PL, 860PP, and 860PM.

FIG. 38A is a planar view of the alternative embodiment of FIG. 37 whichdemonstrates the microelectrode elements (generally 865) in more detail.The microelectrode elements 865 in this embodiment are confined to twoelongated elliptical shapes per protruding shaft 860 and are dedicatedto neural stimulation. However, it is understood, as with previousembodiments, that the geometry, size, and quantity of microelectrodeelements can vary. Additionally, as with previous embodiments, theintended use of the microelectrodes can vary, such as microelectrodeelements 860 that are designed specifically for neural recording. FIG.38B is an additional planar view of the same embodiment.

FIG. 39A is a perspective view of the microelectrode array film 820required in the assembly of the alternative embodiment of FIG. 37. Inthis embodiment an extended portion 828 is used to add additionalmicroelectrode array shafts 861 to the designs of previous embodiments.It is understood to those knowledgeable in the art that the samemicrofabrication and assembly methods are used to implement thisalternative embodiment.

FIG. 39B is a perspective view of the protruding shaft support 880required in the assembly of the alternative embodiment of FIG. 37. Aswith previous embodiments, this shaft support 880 can be cut from ahollow cylinder of material using a laser etch process. Themicroelectrode array film 820 is then assembled onto the surface ofprotruding shaft support 880.

In some embodiments it is advantageous to not require a microelectronicelement 300. This may be the case when using the embodiment in astimulation mode only, or when using low numbers of stimulation sites.FIG. 40A is a perspective view of an alternative embodiment where fiveprotruding shafts 960 are connected directly to the fifteen electricallead wires 990. The distal microelectrode assembly 950 is therefore indirect electrical communication with the proximal electrical contacts.

FIG. 40B is a perspective view of the microelectrode array film 920required in the assembly of the alternative embodiment shown in FIG.40A. In comparison to previous embodiments, it does not have amicroelectronic component platform but instead the microelectrodes areelectrically connected directly to the lead wire contact pads 908.

In some embodiments it is advantageous to not require that theprotruding shafts be rigid, and therefore they do not need to besupported. This may be the case when using the embodiment in delicatetissues. FIG. 40C is a perspective view of an alternative embodimentwhere five protruding shafts 1060 are not supported by a rigid member,but only consist of the microelectrode array film.

FIG. 40D is a detail perspective view of the internal assembly 1020 ofthe alternative embodiment shown in FIG. 40C. In comparison to previousembodiments, it does not require a microelectronic component platformbut instead the microelectrodes are electrically connected directly tothe lead wire contact pads 1008. Furthermore, in comparison to previousembodiments, it does not require a rigid protruding shaft support, butthis has been replaced by a cylindrical support 1080. In the presentembodiment ten lead wires connect directly to ten microelectrodeelements where each flexible shaft 1061 incorporates two microelectrodeelements 1065.

Microelectronic Elements

When the embodiment is in used only for neural recording, themicroelectronic element 300 may be configured to only collectelectrophysiologically recorded data. FIG. 41 demonstrates a schematicof an electronic circuit that could be implemented withinmicroelectronic element 300. Microelectrode elements 365 are in contactwith the neurological tissue. Microelectrode elements 365 are lettered athrough n, with dots in between to describe a finite number of possiblemicroelectrode elements 365. Generally there is at least onemicroelectrode element 365, and in the present embodiment fifteen arerequired. Electrophysiological signals depolarize microelectrodeelements 365 and this signal can be captured by the neural recordingmicroelectronic element 320. The microelectrode element 365 chosen toperform the recording can be selected using switchbox 321. The signal isthen routed to switchbox 322, which can chosen to either amplify localfield potentials using amplifier 324, or spikes using spike amplifier325. The signal may then be encoded for transmission to the distal endof the microelectrode lead assembly 100. Connected to the distal endshould be a decoder 390, and a display, or data capture device, 391. Insome embodiments the circuit can be implemented for each microelectrodeelement 365. Generally, the frequency bandwidth required for therecording is low enough that all microelectrode elements 365 cantime-share the same amplification circuit, whilst display 391 can reportthe recordings simultaneously.

When the embodiment is in used only for neural stimulation, themicroelectronic element 300 may be configured to only generate, oralternatively route, stimulation signals. FIG. 42 demonstrates aschematic of an electronic circuit that could be implemented withinmicroelectronic element 300. Microelectrode elements 365 are in contactwith the neurological tissue. Stimulation signals are used to stimulateor inhibit neuronal activity and the microelectronic circuit 330 canperform the generation, or routing, of stimulation signals. Themicroelectrode element 365 chosen to apply the stimulation signal canselected using switchbox 331. In some embodiments, several switches arechosen in order to apply the same signal to several microelectrodeelements 365. In some embodiments, several unique signals are generated,or routed, and applied to at least one microelectrode element 365. Ifthe stimulation signal is generated outside of the microelectronicelement 300, the signal can be conditioned, and if necessary amplified,using signal conditioner 335. A dedicated lead wire on microelectrodelead assembly 100 can be reserved for this purpose. Additionally,dedicated lead wires on microelectrode lead assembly 100 can be reservedfor supplying power to the microelectronic element 330, clock signals,and ground, and command signals.

In some embodiments the operator wishes to record and stimulate with thesame microelectrode elements. To perform this method microelectronicelement 300 may be implemented with both recording and stimulationfunctions. FIG. 43 demonstrates a schematic of an electronic circuitthat could be implemented within microelectronic element 300.Microelectrode elements 365 are in contact with the neurological tissue.Electrophysiological signals depolarize microelectrode elements 365 andthis signal can be captured by the neural recording and stimulationmicroelectronic element 350. The microelectrode element 365 chosen toperform the recording can be selected using switchbox 351, and switchbox 357 can be selected to the recording state. The signal is thenrouted to switchbox 358, which can chosen to either amplify local fieldpotentials using amplifier 354, or spikes using spike amplifier 353. Thesignal may then be encoded for transmission to the distal end of themicroelectrode lead assembly 100 using encoder 356.

Stimulation signals are used to stimulate or inhibit neuronal activityand the neuronal recording and stimulation microelectronic circuit 350can perform the generation, or routing, of stimulation signals. Themicroelectrode element 365 chosen to apply the stimulation signal can beselected using switchbox 351. In some embodiments, several switches arechosen in order to apply the same signal to several microelectrodeelements 365. Additionally, switchbox 357 can be in the stimulationstate. In some embodiments, several unique signals are generated, orrouted, and applied to at least one microelectrode element 365. If thestimulation signal is generated outside of the microelectronic element300, the signal can be conditioned, and if necessary amplified, usingsignal conditioner 355. A dedicated lead wire on microelectrode leadassembly 100 can be reserved for this purpose. Additionally, someembodiments may include high-pass filters 360, of which each filter isdedicated to an individual microelectrode element 365, or shared betweenseveral microelectrode elements 365. These high-pass filters 360 may beused in order to tune the stimulation signal to the peak resistancefrequency of the microelectrode element 365.

Additionally, dedicated lead wires on microelectrode lead assembly 100can be reserved for supplying power to the neural recording andstimulation microelectronic element 350, clock signals, and ground, andcommand signals, recorded signals, and stimulation signals.

Electrical Impedance Tomography

FIG. 44 demonstrate how Electrical Impedance Tomography may be performedusing the devices described. First, an oscillating current is passedbetween two microelectrode elements 865Ac and 865Pa. The currentoscillation may be of a frequency of 1 Hz-10 MHz with a preference of 1kHz-100 KHz. Additionally, the current oscillation may include otheroscillation frequencies. Subsequently, an electric potential is detectedbetween two other microelectrode elements 865Lc and 865L. Alternatively,the electrode potential can be detected at the site of themicroelectrode elements that generated and collected the current. Thispotential gives an indication of the electrical properties of the imagedtissue. Source and detection electrode are alternated, both in 2D space,and 3D space to generate a volumetric and/or tomographic image of thevolume contained within the prongs. The signals emanating and detectedat the electrodes sites can change in amplitude, frequency, and othercharacteristics in order to image different tissue properties such asconductivity, permittivity, conductivity direction and/or anisotropy.From this electrical data an understanding of the tissue architecturecan be obtained such as location, direction and type of neural fibers,delineation of different tissue types such as grey matter, white matter,and aqueducts, are but a few examples. The image is then reported to theclinician, additionally it can be fitted to known anatomical data inorder to provide a first approximation to the device location. Electrodegeometries on the prongs can vary, including a single linear array ofelectrodes, or electrodes that are side-by-side (not shown).

CONCLUSION

Various embodiments of micro-fabricated neurostimulation devices havebeen described herein. These embodiments are giving by way of exampleand are not intended to limit the scope of the present invention. Itshould be appreciated, moreover, that the various features of theembodiments that have been described may be combined in various ways toproduce numerous additional embodiments. Moreover, while variousmaterials, dimensions, shapes, implantation locations, etc. have beendescribed for use with disclosed embodiments, others besides thosedisclosed may be utilized without exceeding the scope of the invention.

Although some devices described herein are identified as either acute orchronic, it is understood that the device may be used acutely, orchronically. They may be implanted for such periods, such as during asurgery, and then removed. They may implanted for extended periods, oreven indefinitely. Similarly, any devices described herein as beingchronic, it is understood that such devices may also be used acutely.

The present disclosure is not to be limited in terms of the particularembodiments described in this application, which are intended asillustrations of various aspects. Many modifications and variations canbe made without departing from its spirit and scope, as will be apparentto those skilled in the art. Functionally equivalent methods andapparatuses within the scope of the disclosure, in addition to thoseenumerated herein, will be apparent to those skilled in the art from theforegoing descriptions. Such modifications and variations are intendedto fall within the scope of the appended claims. The present disclosureis to be limited only by the terms of the appended claims, along withthe full scope of equivalents to which such claims are entitled. It isto be understood that this disclosure is not limited to particularmethods, reagents, compounds compositions or biological systems, whichcan, of course, vary. It is also to be understood that the terminologyused herein is for the purpose of describing particular embodimentsonly, and is not intended to be limiting.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity.

It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to embodiments containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should be interpreted to mean “at least one”or “one or more”); the same holds true for the use of definite articlesused to introduce claim recitations. In addition, even if a specificnumber of an introduced claim recitation is explicitly recited, thoseskilled in the art will recognize that such recitation should beinterpreted to mean at least the recited number (e.g., the barerecitation of “two recitations,” without other modifiers, means at leasttwo recitations, or two or more recitations). Furthermore, in thoseinstances where a convention analogous to “at least one of A, B, and C,etc.” is used, in general such a construction is intended in the senseone having skill in the art would understand the convention (e.g., “asystem having at least one of A, B, and C” would include but not belimited to systems that have A alone, B alone, C alone, A and Btogether, A and C together, B and C together, and/or A, B, and Ctogether, etc.). In those instances where a convention analogous to “atleast one of A, B, or C, etc.” is used, in general such a constructionis intended in the sense one having skill in the art would understandthe convention (e.g., “a system having at least one of A, B, or C” wouldinclude but not be limited to systems that have A alone, B alone, Calone, A and B together, A and C together, B and C together, and/or A,B, and C together, etc.). It will be further understood by those withinthe art that virtually any disjunctive word and/or phrase presenting twoor more alternative terms, whether in the description, claims, ordrawings, should be understood to contemplate the possibilities ofincluding one of the terms, either of the terms, or both terms. Forexample, the phrase “A or B” will be understood to include thepossibilities of “A” or “B” or “A and B.”

In addition, where features or aspects of the disclosure are describedin terms of Markush groups, those skilled in the art will recognize thatthe disclosure is also thereby described in terms of any individualmember or subgroup of members of the Markush group.

As will be understood by one skilled in the art, for any and allpurposes, such as in terms of providing a written description, allranges disclosed herein also encompass any and all possible subrangesand combinations of subranges thereof. Any listed range can be easilyrecognized as sufficiently describing and enabling the same range beingbroken down into at least equal halves, thirds, quarters, fifths,tenths, etc. As a non-limiting example, each range discussed herein canbe readily broken down into a lower third, middle third and upper third,etc. As will also be understood by one skilled in the art all languagesuch as “up to,” “at least,” “greater than,” “less than,” and the likeinclude the number recited and refer to ranges which can be subsequentlybroken down into subranges as discussed above. Finally, as will beunderstood by one skilled in the art, a range includes each individualmember. Thus, for example, a group having 1-3 cells refers to groupshaving 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers togroups having 1, 2, 3, 4, or 5 cells, and so forth.

One or more or any part thereof of the techniques described herein canbe implemented in computer hardware or software, or a combination ofboth. The methods can be implemented in computer programs using standardprogramming techniques following the method and figures describedherein. Program code is applied to input data to perform the functionsdescribed herein and generate output information. The output informationis applied to one or more output devices such as a display monitor. Eachprogram may be implemented in a high level procedural or object orientedprogramming language to communicate with a computer system. However, theprograms can be implemented in assembly or machine language, if desired.In any case, the language can be a compiled or interpreted language.Moreover, the program can run on dedicated integrated circuitspreprogrammed for that purpose.

Each such computer program is preferably stored on a storage medium ordevice (e.g., ROM or magnetic diskette) readable by a general or specialpurpose programmable computer, for configuring and operating thecomputer when the storage media or device is read by the computer toperform the procedures described herein. The computer program can alsoreside in cache or main memory during program execution. The analysis,preprocessing, and other methods described herein can also beimplemented as a computer-readable storage medium, configured with acomputer program, where the storage medium so configured causes acomputer to operate in a specific and predefined manner to perform thefunctions described herein. In some embodiments, the computer readablemedia is tangible and substantially non-transitory in nature, e.g., suchthat the recorded information is recorded in a form other than solely asa propagating signal.

In some embodiments, a program product may include a signal bearingmedium. The signal bearing medium may include one or more instructionsthat, when executed by, for example, a processor, may provide thefunctionality described above. In some implementations, signal bearingmedium may encompass a computer-readable medium, such as, but notlimited to, a hard disk drive, a Compact Disc (CD), a Digital Video Disk(DVD), a digital tape, memory, etc. In some implementations, the signalbearing medium may encompass a recordable medium, such as, but notlimited to, memory, read/write (R/W) CDs, R/W DVDs, etc. In someimplementations, signal bearing medium may encompass a communicationsmedium such as, but not limited to, a digital and/or an analogcommunication medium (e.g., a fiber optic cable, a waveguide, a wiredcommunications link, a wireless communication link, etc.). Thus, forexample, the program product may be conveyed by an RF signal bearingmedium, where the signal bearing medium is conveyed by a wirelesscommunications medium (e.g., a wireless communications medium conformingwith the IEEE 802.11 standard).

It is to be understood that any of the signals and signal processingtechniques may be digital or analog in nature, or combinations thereof.

While certain embodiments of this invention have been particularly shownand described with references to preferred embodiments thereof, it willbe understood by those skilled in the art that various changes in formand details may be made therein without departing from the scope of theinvention encompassed by the appended claims.

What is claimed is:
 1. An implantable neurological probe, comprising: anelongated shaft having a distal end and an internal lumen; a supportcylinder slidingly disposed in only a distal portion of the internallumen; a plurality of shafts coupled to the support cylinder andarranged for selective extension from the distal end of the elongatedshaft; a microelectrode array film comprising a first portion coupledtoward the distal end of the elongated shaft and a second portioncoupled with the support cylinder, the microelectrode array filmcomprising a plurality of microelectrode film shafts disposed on each ofthe plurality of shafts, each of the plurality of microelectrode filmshafts comprising a plurality of microelectrode elements, themicroelectrode array film further comprising: a helical ribbon cablethat separates the first portion of the microelectrode array film fromthe second portion of the microelectrode array film, the helical ribboncable couples each of the plurality of microelectrode elements with arespective proximal contact pad; a planar substrate having an insulativelayer; and a plurality of conductive traces disposed on the insulativelayer; and a stylet removably disposed in the internal lumen andconfigured to contact the support cylinder to selectively extend theplurality of shafts during implantation.
 2. The implantable neurologicalprobe of claim 1, comprising a push-pull rod which comprises a pull wireand the stylet.
 3. The implantable neurological probe of claim 1,wherein the elongated shaft is configured for insertion into a humanbody using an accepted procedure for insertion of deep brain stimulationleads.
 4. The implantable neurological probe of claim 1, wherein adiameter of the elongated shaft is between 1 mm and 3 mm.
 5. Theimplantable neurological probe of claim 1, wherein at least one of theplurality of microelectrode elements is a stimulating electrode and atleast one of the plurality of microelectrode elements is a detectingelectrode.
 6. The implantable neurological probe of claim 1, wherein atleast one of the plurality of microelectrodes elements is both astimulating electrode and a detecting electrode.
 7. The implantableneurological probe of claim 1, wherein each of the plurality ofmicroelectrode elements is disposed on the insulative layer.
 8. Theimplantable neurological probe of claim 7, wherein the microelectrodearray film is formable into a cylindrical assembly.
 9. The implantableneurological probe of claim 8, wherein each of the plurality of shaftscan be formed to bend radially from a longitudinal axis of the elongatedshaft.
 10. The implantable neurological probe of claim 8, where one ofthe plurality of shafts extends and is centered along a longitudinalaxis of the elongated shaft.
 11. The implantable neurological probe ofclaim 9, where each of the plurality of microelectrode film shafts arestiffened by one of the plurality of shafts.
 12. An implantableneurological probe, comprising: an elongated shaft having a distal endand an internal lumen; a plurality of shafts coupled to a supportcylinder, the plurality of shafts arranged for selective extension fromthe distal end of the elongated shaft; and a microelectrode array filmcomprising a first portion coupled toward the distal end of theelongated shaft and a second portion coupled with the support cylinder,the microelectrode array film comprising a plurality of microelectrodefilm shafts disposed on each of the plurality of shafts, each of theplurality of microelectrode film shafts comprising a plurality ofmicroelectrode elements, the microelectrode array film furthercomprising: a helical ribbon cable separating the first portion of themicroelectrode array film from the second portion of the microelectrodearray film, the helical ribbon cable coupling each of the plurality ofmicroelectrode elements with a respective proximal contact pad; a planarsubstrate having an insulative layer; and a plurality of conductivetraces disposed on the insulative layer, wherein the plurality of shaftsdefine a substantially cylindrical volume when fully extended.
 13. Theimplantable neurological probe of claim 12, wherein the elongated shaftis configured for insertion into a human body using an acceptedprocedure for insertion of deep brain stimulation leads.
 14. Theimplantable neurological probe of claim 12, wherein a diameter of theelongated shaft is between 1 mm and 3 mm.
 15. The implantableneurological probe of claim 12, wherein at least one of the plurality ofmicroelectrode elements is a stimulating electrode and at least one ofthe plurality of microelectrode elements is a detecting electrode. 16.The implantable neurological probe of claim 12, wherein at least one ofthe plurality of microelectrodes elements is both a stimulatingelectrode and a detecting electrode.
 17. The implantable neurologicalprobe of claim 12, wherein each of the plurality of microelectrodeelements is disposed on the insulative layer.
 18. The implantableneurological probe of claim 17, wherein the microelectrode array film isformable into a cylindrical assembly.
 19. The implantable neurologicalprobe of claim 18, where at least one of the plurality of shafts can beformed to bend radially from a longitudinal axis of the elongated shaft.20. The implantable neurological probe of claim 18, where one of theplurality of shafts is centered along a longitudinal axis of theelongated shaft.
 21. The implantable neurological probe of claim 18,where each of the plurality of microelectrode shafts are stiffened byone of the plurality of shafts.
 22. A method of finding a neurologicaltarget, comprising: implanting a neurological probe within a vicinity ofa neurological target site, the neurological probe comprising: anelongated shaft having a distal end and an internal lumen; a supportcylinder slidingly disposed in only a distal portion of the internallumen; a plurality of shafts coupled to the support cylinder andarranged for selective extension from the distal end of the elongatedshaft; a microelectrode array film comprising a first portion coupledtoward the distal end of the elongated shaft and a second portioncoupled with the support cylinder, the microelectrode array filmcomprising a plurality of microelectrode film shafts disposed on each ofthe plurality of shafts, each of the plurality of microelectrode filmshafts comprising a plurality of microelectrode elements, themicroelectrode array film further comprising: a helical ribbon cableseparating the first portion of the microelectrode array film from thesecond portion of the microelectrode array film, the helical ribboncable coupling each of the plurality of microelectrode elements with arespective proximal contact pad; a planar substrate having an insulativelayer; and a plurality of conductive traces disposed on the insulativelayer; and a stylet removably disposed in the internal lumen andconfigured to contact the support cylinder to selectively extend theplurality of shafts during implantation; retracting the plurality ofshafts within the internal lumen before surgical implantation; extendingthe plurality of shafts in the vicinity of the neurological target sitefollowing implantation; recording electrophysiological signals from theneurological target site using at least one of the plurality ofmicroelectrode elements; and stimulating the neurological target usingat least one of the plurality of microelectrode elements.
 23. The methodof claim 22, further comprising: after the acts of recording andstimulating, retracting the plurality of shafts within the internallumen and removing the neurological probe from a subject.
 24. The methodof claim 22, wherein the plurality of shafts are retracted using a pullwire.
 25. The method of claim 22, wherein the plurality of shafts areextended using the stylet.
 26. The method of claim 22, wherein theneurological probe comprises a push-pull rod which comprises a pull wireand the stylet.
 27. The method of claim 22, wherein the act of recordingneurophysiological signals comprises recording neural activity detectedby at least one of the plurality of microelectrode elements andrepositioning the distal end of the elongated shaft as required, untilthe recorded activity is indicative of the distal end of the elongatedprobe shaft being located sufficiently at the neurological target site.28. The method of claim 22, comprising: stimulating neural activity at astimulation site by applying electrical signals to at least one of theplurality of microelectrode elements; performing a clinical evaluationof the efficacy on the stimulation site in a patient, and repositioningthe distal end of the elongated shaft as required, until the patient'sresponse is indicative of the distal end of the elongated shaft beinglocated sufficiently at the neurological target site.
 29. The method ofclaim 22, comprising: inhibiting neural activity by applying electricalsignals to at least one of the plurality of microelectrode, performing aclinical evaluation of the efficacy on the inhibition site in a patient,and repositioning the distal end of elongated shaft as required, untilthe patient's response is indicative of the distal end of the elongatedshaft being located sufficiently at the neurological target site.
 30. Amethod of finding a neurological target, comprising: implanting aneurological probe within a vicinity of a neurological target site, theneurological probe comprising: an elongated shaft having a distal endand an internal lumen; a support cylinder slidingly disposed in only adistal portion of the internal lumen; a plurality of shafts coupled tothe support cylinder and arranged for selective extension from thedistal end of the elongated shaft; a microelectrode array filmcomprising a first portion coupled toward the distal end of theelongated shaft and a second portion coupled with the support cylinder,the microelectrode array film comprising a plurality of microelectrodefilm shafts disposed on each of the plurality of shafts, each of theplurality of microelectrode film shafts comprising a plurality ofmicroelectrode elements, the microelectrode array film furthercomprising: a helical ribbon cable separating the first portion of themicroelectrode array film from the second portion of the microelectrodearray film, the helical ribbon cable coupling each of the plurality ofmicroelectrode elements with a respective proximal contact pad; a planarsubstrate having an insulative layer; and a plurality of conductivetraces disposed on the insulative layer; and a stylet removably disposedin the internal lumen and configured to contact the support cylinder toselectively extend the plurality of shafts during implantation;retracting the plurality of shafts within the internal lumen beforesurgical implantation; expanding the plurality of shafts in the vicinityof the neurological target site following implantation; applying anoscillating electric current between at least two of the plurality ofmicroelectrode elements; and detecting an electric voltage between atleast two of the plurality of microelectrode elements.
 31. The method ofclaim 30, further comprising: after the act of detecting, retracting theplurality of shafts within the internal lumen and removing theneurological probe from a subject.
 32. The method of claim 30,comprising imaging the electrical characteristics of the volume ofneurological tissue between the plurality of shafts based on the appliedoscillating electric current and the detected electric voltage.
 33. Themethod of claim 30, wherein the neurological probe comprises a push-pullrod which comprises a pull wire and the stylet.
 34. A method of findinga neurological target, comprising: implanting a neurological probewithin a vicinity of a neurological target site, the neurological probecomprising: an elongated shaft having a distal end and an internallumen; a plurality of shafts coupled to a support cylinder, theplurality of shafts arranged for selective extension from the distal endof the elongated shaft; and a microelectrode array film comprising afirst portion coupled toward the distal end of the elongated shaft and asecond portion coupled with the support cylinder, the microelectrodearray film comprising a plurality of microelectrode film shafts disposedon each of the plurality of shafts, each of the plurality ofmicroelectrode film shafts comprising a plurality of microelectrodeelements, the microelectrode array film further comprising: a helicalribbon cable separating the first portion of the microelectrode arrayfilm from the second portion of the microelectrode array film, thehelical ribbon cable coupling each of the plurality of microelectrodeelements with a respective proximal contact pad; a planar substratehaving an insulative layer; and a plurality of conductive tracesdisposed on the insulative layer; and wherein the plurality of shaftsdefine a substantially cylindrical volume when fully extended;retracting the plurality of shafts within the internal lumen beforesurgical implantation; extending the plurality of shafts in the vicinityof the neurological target site following implantation; recordingelectrophysiological signals from the neurological target site using atleast one of the plurality of microelectrode elements; and stimulatingthe neurological target using at least one of the plurality ofmicroelectrode elements.
 35. The method of claim 34, wherein theprotruding shafts are retracted using a pull wire.
 36. The method ofclaim 35, wherein the plurality of shafts are extended using a stylet.37. The method of claim 36, wherein the neurological probe comprises apush-pull rod which comprises the pull wire and the stylet.
 38. Themethod of claim 34, wherein the act of recording neurophysiologicalsignals comprises recording neural activity detected by at least one ofthe plurality of microelectrode elements and repositioning the distalend of the elongated shaft as required, until the recorded activity isindicative of the distal end of the elongated probe shaft being locatedsufficiently at the neurological target site.
 39. The method of claim34, further comprising: after the acts of recording and stimulating,retracting the plurality of shafts within the internal lumen andremoving the neurological probe from a subject.
 40. The method of claim34, comprising: stimulating neural activity at a stimulation site byapplying electrical signals to at least one of the plurality ofmicroelectrode elements; performing a clinical evaluation of theefficacy on the stimulation site in a patient, and repositioning thedistal end of the elongated shaft as required, until the patient'sresponse is indicative of the distal end of the elongated shaft beinglocated sufficiently at the neurological target site.
 41. The method ofclaim 34, comprising: inhibiting neural activity by applying electricalsignals to at least one of the plurality of microelectrode elements;performing a clinical evaluation of the efficacy on the inhibition sitein a patient, and repositioning the distal end of elongated shaft asrequired, until the patient's response is indicative of the distal endof the elongated shaft being located sufficiently at the neurologicaltarget site.
 42. A method of finding a neurological target, comprising:implanting a neurological probe within a vicinity of a neurologicaltarget site, the neurological probe comprising: an elongated shafthaving a distal end and an internal lumen; a plurality of shafts coupledto a support cylinder, the plurality of shafts arranged for selectiveextension from the distal end of the elongated shaft; and amicroelectrode array film comprising a first portion coupled toward thedistal end of the elongated shaft and a second portion coupled with thesupport cylinder, the microelectrode array film comprising a pluralityof microelectrode film shafts disposed on each of the plurality ofshafts, each of the plurality of microelectrode film shafts comprising aplurality of microelectrode elements, the microelectrode array filmfurther comprising: a helical ribbon cable separating the first portionof the microelectrode array film from the second portion of themicroelectrode array film, the helical ribbon cable coupling each of theplurality of microelectrode elements with a respective proximal contactpad; a planar substrate having an insulative layer; and a plurality ofconductive traces disposed on the insulative layer, wherein theplurality of shafts define a substantially cylindrical volume when fullyextended; retracting the plurality of shafts within the internal lumenbefore surgical implantation; extending the plurality of shafts in thevicinity of the neurological target site following implantation;applying an oscillating electric current between at least two of theplurality of microelectrode elements on at least one of the plurality ofshafts; detecting an electric voltage between at least two of theplurality of microelectrode elements on at least one of the plurality ofshafts.
 43. The method of claim 42, comprising imaging the electricalcharacteristics of the volume of neurological tissue between theplurality of shafts based on the applied oscillating electric currentand the detected electric voltage.
 44. The method of claim 32, furthercomprising: after the act of detecting, retracting the plurality ofshafts within the internal lumen and removing the neurological probefrom a subject.